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Association of CYP2D6 metabolizer status with mammographic density change in response to tamoxifen treatment

INTRODUCTION: Not all breast cancer patients respond to tamoxifen treatment, possibly due to genetic predisposition. As tamoxifen-induced reductions in percent mammographic density (PMD) have been linked to the risk and prognosis of breast cancer, we conducted a candidate gene study to investigate t...

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Detalles Bibliográficos
Autores principales: Li, Jingmei, Czene, Kamila, Brauch, Hiltrud, Schroth, Werner, Saladores, Pilar, Li, Yi, Humphreys, Keith, Hall, Per
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3979120/
https://www.ncbi.nlm.nih.gov/pubmed/24088226
http://dx.doi.org/10.1186/bcr3495
Descripción
Sumario:INTRODUCTION: Not all breast cancer patients respond to tamoxifen treatment, possibly due to genetic predisposition. As tamoxifen-induced reductions in percent mammographic density (PMD) have been linked to the risk and prognosis of breast cancer, we conducted a candidate gene study to investigate the association between germline CYP2D6 polymorphisms and PMD change. METHODS: Baseline and follow-up mammograms were retrieved for 278 tamoxifen-treated subjects with CYP2D6 metabolizer status (extensive (EM), heterozygous extensive/intermediate (hetEM/IM) or poor metabolizer (PM)). Logistic regression analyses were conducted comparing subjects who experienced >10% reduction in PMD to those who experienced ≤10% reduction or increase. RESULTS: After multivariate adjustment, PMD change was found to be significantly associated with the degree of CYP2D6 enzyme functionality (Ptrend = 0.021). Compared with EM, hetEM/IM and PM were 72% (95% confidence interval (CI): 0.10 to 0.79) and 71% (0.03 to 2.62) less likely to experience a >10% reduction, respectively. CONCLUSIONS: Tamoxifen-induced change in PMD appears to have a genetic component.